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School of Medicine
Department Affiliation: Primary: National Institute on Aging,
Laboratory of Clinical Investigation; Secondary: Pharmacology and Molecular Sciences, Medicine (Geriatrics)
Degree: M.D., Ph.D., University of Kansas School of Medicine
Rank: Lab Chief, Professor
Telephone Number: 410-558-8611
Fax Number: 410-558-8318
E-mail address: AbernethyD@grc.nia.nih.gov
School of Medicine Address: Gerontology Research Center,
5600 Nathan Shock Drive, Baltimore, MD 21224-6825
The Laboratory of Clinical Investigation (LCI) has been organized into 6 sections (Molecular and Clinical Pharmacology, Diabetes, Metabolism, Longitudinal Studies, Hematology and Oncology, and the newly formed Bioanalytical and Drug Discovery Section), with one operating unit (Nuclear Magnetic Resonance).
The overall goals of the Laboratory of Clinical Investigation are (1) to gain fundamental understanding of age and disease related changes (a) in calcium ion channel function; (b) islet cell differentiation and insulin secretion; (c) insulin receptor function; (d) molecular and cellular changes in osteoarthritis; and (d) genetic features of tumorigenesis: (2) to carry out translational research in each of these areas to apply hypotheses generated from fundamental studies to humans in health and disease: (3) to identify therapeutic targets in each of these areas and in other laboratories across the NIA-IRP: and (4) to develop therapeutic agents for the identified targets and carry out preclinical and clinical studies for proof of principle for the targets. To meet these objectives, studies are performed at the molecular, cellular, animal model, and human levels. To support the objectives, the physical sciences (In vivo nuclear magnetic resonance, bioanalytical separation and analytic techniques) are brought to bear as well as the more usual biological sciences. This permits asking questions “at the cutting edge” to achieve the above goals. For example, the best (but rarely used) method of characterizing genetically altered mice (transgenic) is nuclear magnetic resonance. This is used across the laboratory (and is a resource to the whole NIA-IRP) to understand the role of specific genetic changes in whole animal physiology. In the same manner, to understand post genetic alterations in cellular constituents, the emerging science of proteomics is assuming great importance. The Bioanalytical/Drug Discovery Section, using the best tools for protein analysis such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and capillary electrophoresis/laser induced fluorescence (CE-LIF) offers all LCI sections, and the NIA-IRP, the opportunity to be at the leading edge of research to understand the contribution of post-genetic protein alterations as well as genomic variability to better understand diversity in cellular function in health and disease.
The diversity of research areas is a great strength in that potential cross discipline collaborations become obvious and are encouraged and facilitated in the laboratory. These interdisciplinary activities often extend into other laboratories and to extramural investigators as well. Therefore each investigator functions independently in their own area of interest, and at the same time has the opportunity to extend and leverage their expertise to other investigative areas, enhancing the creative and productive potential of each investigator and the laboratory.
- Urquidi-Macdonald, M., Mager, D.E., Mascelli, M.A., Frederick, B., Freedman, J., Fitzgerald, D.J., Kleiman, N.S., and Abernethy, D.R. Abciximab pharmacodynamic model using neural networks to integrate sources of patient variability, Clin. Pharmacol. Ther. 75:60-69, 2004. Pub Med Reference
- Mager, D.E., Merritt, M.M., Kasturi, J., Witkin, L.R., Urdiqui-Macdonald, M., Sollers, J.J., Evans, M.K., Zonderman, A.B., Abernethy, D.R., and Thayer, J.F. Kullback-Leibler clustering of continuous wavelet transform measures of heart rate variability, Biomed. Sci. Instrum. 40:337-342, 2004. Pub Med Reference
- Kobrinsky, E., Kepplinger, K.J.F., Yu, A., Harry, J.B., Kahr, H., Romanin, C., Abernethy, D.R., and Soldatov, N.M. Voltage-gated rearrangements associated with differential b-subunit modulation of the L-type Ca2+ channel inactivation, Biophys. J. 87:844-857, 2004. Pub Med Reference
- Mager, D.E., Abernethy, D.R., Egan, J.M., and Elahi, D. Exendin-4 pharmacodynamics: Insights from the hyperglycemic clamp techniquem, J. Pharmacol. Exp. Ther. 311:830-835, 2004. Pub Med Reference
- Harry, J.B., Kobrinsky, E., Abernethy, D.R., and Soldatov, N.M. New short splice variants of the human cardiac Cavbeta 2 subunit: Redefining the major functional motifs implemented in modulation of the Cav1.2 channel, J. Biol. Chem. 279:46367-46372, 2004. Pub Med Reference
- Kobrinsky, E., Tiwari, S., Maltsev, V., Harry, J.B., Lakatta, E., Abernethy, D.R., and Soldatov, N.M. Differential role of the alpha 1C subunit tails in regulation of the Cav1.2 channel by membrane potential, beta subunits and Ca2+ ions. J. Biol. Chem. 280:12474-12486, 2005. Pub Med Reference
- Kobrinsky, E., Mager, D.E., Bentil, S.A., Murata, S.L., Abernethy, D.R., Soldatov, N.M. Identification of plasma membrane macro- and micro-domains from wavelet analysis of FRET microscopy, Biophys. J. 88:3625-3634, 2005. Pub Med Reference
- Mager, D.E., Shirey, J.D., Cox, D., Fitzgerald, D.J., and Abernethy, D.R. Mapping the dose-effect relationship of orbofiban from sparse data with an artificial neural network, J. Pharm. Sci. 94:2475-2486, 2005. Pub Med Reference